Compartmentalization of Total and Virus-Specific Tissue-Resident Memory CD8+ T Cells in Human Lymphoid Organs.
Disruption of T cell memory during severe immune suppression results in reactivation of chronic viral infections, such as Epstein Barr virus (EBV) and Cytomegalovirus (CMV). How different subsets of memory T cells contribute to the protective immunity against these viruses remains poorly defined. In...
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| Language: | English |
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Public Library of Science (PLoS)
2016-08-01
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| Series: | PLoS Pathogens |
| Online Access: | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1005799&type=printable |
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| author | Heng Giap Woon Asolina Braun Jane Li Corey Smith Jarem Edwards Frederic Sierro Carl G Feng Rajiv Khanna Michael Elliot Andrew Bell Andrew D Hislop Stuart G Tangye Alan B Rickinson Thomas Gebhardt Warwick J Britton Umaimainthan Palendira |
| author_facet | Heng Giap Woon Asolina Braun Jane Li Corey Smith Jarem Edwards Frederic Sierro Carl G Feng Rajiv Khanna Michael Elliot Andrew Bell Andrew D Hislop Stuart G Tangye Alan B Rickinson Thomas Gebhardt Warwick J Britton Umaimainthan Palendira |
| author_sort | Heng Giap Woon |
| collection | DOAJ |
| description | Disruption of T cell memory during severe immune suppression results in reactivation of chronic viral infections, such as Epstein Barr virus (EBV) and Cytomegalovirus (CMV). How different subsets of memory T cells contribute to the protective immunity against these viruses remains poorly defined. In this study we examined the compartmentalization of virus-specific, tissue resident memory CD8+ T cells in human lymphoid organs. This revealed two distinct populations of memory CD8+ T cells, that were CD69+CD103+ and CD69+CD103-, and were retained within the spleen and tonsils in the absence of recent T cell stimulation. These two types of memory cells were distinct not only in their phenotype and transcriptional profile, but also in their anatomical localization within tonsils and spleen. The EBV-specific, but not CMV-specific, CD8+ memory T cells preferentially accumulated in the tonsils and acquired a phenotype that ensured their retention at the epithelial sites where EBV replicates. In vitro studies revealed that the cytokine IL-15 can potentiate the retention of circulating effector memory CD8+ T cells by down-regulating the expression of sphingosine-1-phosphate receptor, required for T cell exit from tissues, and its transcriptional activator, Kruppel-like factor 2 (KLF2). Within the tonsils the expression of IL-15 was detected in regions where CD8+ T cells localized, further supporting a role for this cytokine in T cell retention. Together this study provides evidence for the compartmentalization of distinct types of resident memory T cells that could contribute to the long-term protection against persisting viral infections. |
| format | Article |
| id | doaj-art-552bcd3b75c8474db486435ca84dbb1b |
| institution | OA Journals |
| issn | 1553-7366 1553-7374 |
| language | English |
| publishDate | 2016-08-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj-art-552bcd3b75c8474db486435ca84dbb1b2025-08-20T02:03:19ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742016-08-01128e100579910.1371/journal.ppat.1005799Compartmentalization of Total and Virus-Specific Tissue-Resident Memory CD8+ T Cells in Human Lymphoid Organs.Heng Giap WoonAsolina BraunJane LiCorey SmithJarem EdwardsFrederic SierroCarl G FengRajiv KhannaMichael ElliotAndrew BellAndrew D HislopStuart G TangyeAlan B RickinsonThomas GebhardtWarwick J BrittonUmaimainthan PalendiraDisruption of T cell memory during severe immune suppression results in reactivation of chronic viral infections, such as Epstein Barr virus (EBV) and Cytomegalovirus (CMV). How different subsets of memory T cells contribute to the protective immunity against these viruses remains poorly defined. In this study we examined the compartmentalization of virus-specific, tissue resident memory CD8+ T cells in human lymphoid organs. This revealed two distinct populations of memory CD8+ T cells, that were CD69+CD103+ and CD69+CD103-, and were retained within the spleen and tonsils in the absence of recent T cell stimulation. These two types of memory cells were distinct not only in their phenotype and transcriptional profile, but also in their anatomical localization within tonsils and spleen. The EBV-specific, but not CMV-specific, CD8+ memory T cells preferentially accumulated in the tonsils and acquired a phenotype that ensured their retention at the epithelial sites where EBV replicates. In vitro studies revealed that the cytokine IL-15 can potentiate the retention of circulating effector memory CD8+ T cells by down-regulating the expression of sphingosine-1-phosphate receptor, required for T cell exit from tissues, and its transcriptional activator, Kruppel-like factor 2 (KLF2). Within the tonsils the expression of IL-15 was detected in regions where CD8+ T cells localized, further supporting a role for this cytokine in T cell retention. Together this study provides evidence for the compartmentalization of distinct types of resident memory T cells that could contribute to the long-term protection against persisting viral infections.https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1005799&type=printable |
| spellingShingle | Heng Giap Woon Asolina Braun Jane Li Corey Smith Jarem Edwards Frederic Sierro Carl G Feng Rajiv Khanna Michael Elliot Andrew Bell Andrew D Hislop Stuart G Tangye Alan B Rickinson Thomas Gebhardt Warwick J Britton Umaimainthan Palendira Compartmentalization of Total and Virus-Specific Tissue-Resident Memory CD8+ T Cells in Human Lymphoid Organs. PLoS Pathogens |
| title | Compartmentalization of Total and Virus-Specific Tissue-Resident Memory CD8+ T Cells in Human Lymphoid Organs. |
| title_full | Compartmentalization of Total and Virus-Specific Tissue-Resident Memory CD8+ T Cells in Human Lymphoid Organs. |
| title_fullStr | Compartmentalization of Total and Virus-Specific Tissue-Resident Memory CD8+ T Cells in Human Lymphoid Organs. |
| title_full_unstemmed | Compartmentalization of Total and Virus-Specific Tissue-Resident Memory CD8+ T Cells in Human Lymphoid Organs. |
| title_short | Compartmentalization of Total and Virus-Specific Tissue-Resident Memory CD8+ T Cells in Human Lymphoid Organs. |
| title_sort | compartmentalization of total and virus specific tissue resident memory cd8 t cells in human lymphoid organs |
| url | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1005799&type=printable |
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